⌘+K

Pulse Explore Communities Researchers Journals

Home Communities Explore

October 16, 2004Journal of Medicinal ChemistryOpen Access

An Orally Bioavailable, Functionally Selective Inverse Agonist at the Benzodiazepine Site of GABAA α5 Receptors with Cognition Enhancing Properties

Mark S. Chambers John Atack Robert W. Carling Neil Collinson Susan M. Cook Gerard R. Dawson Pushpindar Ferris Sarah C. Hobbs Desmond O’Connor George Marshall Wayne Rycroft Angus M. MacLeod

View Full Paper

Ask AI

Bookmark

Share

Abstract

This is the authors' abstract. We don't add key points for this paper.

(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (13) has been identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5 receptors. 13 is orally bioavailable, readily penetrates the CNS, and enhances performance in animal models of cognition. It does not exhibit the convulsant, proconvulsant, or anxiogenic activity associated with nonselective GABA(A) inverse agonists.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Chambers et al. (2004) studied this question.

synapsesocial.com/papers/6a6f68de8031ec7bb1dbbc62 https://doi.org/10.1021/jm040863t

View Full Paper

Ask AI

Bookmark

Share

Keep reading

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

1Synthesis and Biological Evaluation of 3-Heterocyclyl-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-<i>a</i>]phthalazines and Analogues as Subtype-Selective Inverse Agonists for the GABA<sub>A</sub>α5 Benzodiazepine Binding SiteOriginal Research · 2004 · 70 citations
2Imidazo[1,2<i>-a</i>]pyrimidines as Functionally Selective and Orally Bioavailable GABA<sub>A</sub>α2/α3 Binding Site Agonists for the Treatment of Anxiety DisordersOriginal Research · 2005 · 136 citations
3Synthesis and Characterization of a Novel γ-Aminobutyric Acid Type A (GABAA) Receptor Ligand That Combines Outstanding Metabolic Stability, Pharmacokinetics, and Anxiolytic EfficacyOriginal Research · 2016 · 49 citations
45-(4-Hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7-phenyl-2,3,6,7-tetrahydro1,4-thiazepines as compounds with high affinity at the benzodiazepine binding site on GABAA receptorsOriginal Research · 2011
5Benzodiazepines and GABA A receptor subtypes: Effects in open-field, elevated plus maze-discriminative avoidance task, and conditioned place preference in male miceOriginal Research · 2026

Discovery of Functionally Selective 7,8,9,10-Tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-<i>a</i>]phthalazines as GABA<sub>A</sub>Receptor Agonists at the α<sub>3</sub>Subunit2005
Pharmacology of the β‐Carboline FG‐7142, a Partial Inverse Agonist at the Benzodiazepine Allosteric Site of the GABAA Receptor: Neurochemical, Neurophysiological, and Behavioral Effects2007
New Insight into the Central Benzodiazepine Receptor–Ligand Interactions: Design, Synthesis, Biological Evaluation, and Molecular Modeling of 3-Substituted 6-Phenyl-4H-imidazo[1,5-a][1,4]benzodiazepines and Related Compounds2011
Salicylamides as RNA-Dependent RNA Polymerase Inhibitors with Antiviral Activity against West Nile and Zika VirusesJournal of Medicinal Chemistry · 2026
Chemical Determinants of Spinal Analgesia in NTS2-Selective MacrocyclesJournal of Medicinal Chemistry · 2026

More from Journal of Medicinal Chemistry